Denitsa Docheva

Prof. Dr. Denitsa Docheva

Experimental Trauma Surgery, Department of Trauma Surgery, University Regensburg Medical Centre
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Research Focus & Metrics

Academic Career Length

28Years (1999-Present)

(Calculated once Scilit publication data is synced: current year − year of first publication + 1)

Representative Publications

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1 April 2015 in Advanced Drug Delivery Reviews
Verified
Journal Article
Open access
Denitsa DochevaDenitsa Docheva
Denitsa Docheva
SMSebastian A. Müller
Sebastian A. Müller
MMMartin Majewski
Martin Majewski
CEChristopher H. Evans
Christopher H. Evans
Tendon injuries are common and present a clinical challenge to orthopedic surgery mainly because these injuries often respond poorly to treatment and require prolonged rehabilitation. Therapeutic options used to repair ruptured tendons have consisted of suture, autografts, allografts, and synthetic prostheses. To date, none of these alternatives has provided a successful long-term solution, and often the restored tendons do not recover their complete strength and functionality. Unfortunately, our understanding of tendon biology lags far behind that of other musculoskeletal tissues, thus impeding the development of new treatment options for tendon conditions. Hence, in this review, after introducing the clinical significance of tendon diseases and the present understanding of tendon biology, we describe and critically assess the current strategies for enhancing tendon repair by biological means. These consist mainly of applying growth factors, stem cells, natural biomaterials and genes, alone or in combination, to the site of tendon damage. A deeper understanding of how tendon tissue and cells operate, combined with practical applications of modern molecular and cellular tools could provide the long awaited breakthrough in designing effective tendon-specific therapeutics and overall improvement of tendon disease management.

1 January 2005 in Molecular and Cellular Biology
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Journal Article
Open access
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Denitsa DochevaDenitsa Docheva
Denitsa Docheva
EHErnst B. Hunziker
Ernst B. Hunziker
RFReinhard Fässler
Reinhard Fässler
OBOliver Brandau
Oliver Brandau
Tenomodulin (Tnmd) is a member of a new family of type II transmembrane glycoproteins. It is predominantly expressed in tendons, ligaments, and eyes, whereas the only other family member, chondromodulin I (ChM-I), is highly expressed in cartilage and at lower levels in the eye and thymus. The C-terminal extracellular domains of both proteins were shown to modulate endothelial-cell proliferation and tube formation in vitro and in vivo. We analyzed Tnmd function in vivo and provide evidence that Tnmd is processed in vivo and that the proteolytically cleaved C-terminal domain can be found in tendon extracts. Loss of Tnmd expression in gene targeted mice abated tenocyte proliferation and led to a reduced tenocyte density. The deposited amounts of extracellular matrix proteins, including collagen types I, II, III, and VI and decorin, lumican, aggrecan, and matrilin-2, were not affected, but the calibers of collagen fibrils varied significantly and exhibited increased maximal diameters. Tnmd-deficient mice did not have changes in tendon vessel density, and mice lacking both Tnmd and ChM-I had normal retinal vascularization and neovascularization after oxygen-induced retinopathy. These results suggest that Tnmd is a regulator of tenocyte proliferation and is involved in collagen fibril maturation but do not confirm an in vivo involvement of Tnmd in angiogenesis.

1 April 2003 in Genes & Development
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Journal Article
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TSTakao Sakai
Takao Sakai
SLShaohua Li
Shaohua Li
Denitsa DochevaDenitsa Docheva
Denitsa Docheva
CGCarsten Grashoff
Carsten Grashoff
KSKeiko Sakai
Keiko Sakai
RFReinhard Fässler
Reinhard Fässler
Integrin-mediated cell–matrix interactions are essential for development, tissue homeostasis, and repair. Upon ligand binding, integrins are recruited into focal adhesions (FAs). Integrin-linked kinase (ILK) is an FA component that interacts with the cytoplasmic domains of integrins, recruits adaptor proteins that link integrins to the actin cytoskeleton, and phosphorylates the serine/threonine kinases PKB/Akt and GSK-3β. Here we show that mice lacking ILK expression die at the peri-implantation stage because they fail to polarize their epiblast and to cavitate. The impaired epiblast polarization is associated with abnormal F-actin accumulation at sites of integrin attachments to the basement membrane (BM) zone. Likewise, ILK-deficient fibroblasts showed abnormal F-actin aggregates associated with impaired cell spreading and delayed formation of stress fibers and FAs. Finally, ILK-deficient fibroblasts have diminished proliferation rates. However, insulin or PDGF treatment did not impair phosphorylation of PKB/Akt and GSK-3β, indicating that the proliferation defect is not due to absent or reduced ILK-mediated phosphorylation of these substrates in vivo. Furthermore, expression of a mutant ILK lacking kinase activity and/or paxillin binding in ILK-deficient fibroblasts can rescue cell spreading, F-actin organization, FA formation, and proliferation. Altogether these data show that mammalian ILK modulates actin rearrangements at integrin-adhesion sites.

1 January 2007 in Journal of Cellular and Molecular Medicine
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Journal Article
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Denitsa DochevaDenitsa Docheva
Denitsa Docheva
CPCvetan Popov
Cvetan Popov
WMWolf Mutschler
Wolf Mutschler
MSMatthias Schieker
Matthias Schieker
Mesenchymal stem cells and their clinical relevance Integrins and their importance Cell surface molecules on MSCs Integrin system of MSCs Engagement of integrins in MSC differentiation, attachment to coating materials, survival on scaffolds and neoplastic transformation Conclusions The identification of mesenchymal stem cells (MSCs) in adult human tissues and the disclosure of their self‐renew‐al and multi‐lineage differentiation capabilities have provided exciting prospects for cell‐based regeneration and tis‐sue engineering. Although a considerable amount of data is available describing MSCs, there is still lack of information regarding the molecular mechanisms that govern their adhesion and migration. In this work, we will review the current state of knowledge on integrins and other adhesion molecules found to be expressed on MSCs. The dis‐cussed topics include the characteristics of MSCs and their clinical applications, integrins and their central role in cell‐matrix attachment and migration, and comments on mobilization, differentiation and contribution to tumour development. Finally, by understanding the complex and fundamental pathways by which MSCs attach and migrate, it might be possible to fine‐tune the strategies for effective and safe use of MSCs in regenerative therapies.

10 September 2020 in RSC Advances
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Journal Article
Open access
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Kalim DeshmukhKalim Deshmukh
Kalim Deshmukh
Tomáš KováříkTomáš Kovářík
Tomáš Kovářík
TKTomáš Křenek
Tomáš Křenek
Denitsa DochevaDenitsa Docheva
Denitsa Docheva
TSTheresia Stich
Theresia Stich
JPJosef Pola
Josef Pola
Sol–gel derived bioactive glasses have been extensively explored as a promising and highly porous scaffold materials for bone tissue regeneration applications owing to their exceptional osteoconductivity, osteostimulation and degradation rates.

1 July 2017 in EFORT Open Reviews
Verified
Journal Article
Open access
FWFan Wu
Fan Wu
MNMichael Nerlich
Michael Nerlich
Denitsa DochevaDenitsa Docheva
Denitsa Docheva
Tendons connect muscles to bones, ensuring joint movement. With advanced age, tendons become more prone to degeneration followed by injuries. Tendon repair often requires lengthy periods of rehabilitation, especially in elderly patients. Existing medical and surgical treatments often fail to regain full tendon function. The development of novel treatment methods has been hampered due to limited understanding of basic tendon biology. Recently, it was discovered that tendons, similar to other mesenchymal tissues, contain tendon stem/progenitor cells (TSPCs) which possess the common stem cell properties. The current strategies for enhancing tendon repair consist mainly of applying stem cells, growth factors, natural and artificial biomaterials alone or in combination. In this review, we summarise the basic biology of tendon tissues and provide an update on the latest repair proposals for tendon tears. Cite this article: EFORT Open Rev 2017;2:332-342. DOI: 10.1302/2058-5241.2.160075